1 Field of the Invention
The present invention is in the field of medical imaging including computerized tomography (CT), magnetic resonance imaging (MRI), general and/or digital radiography, or the like, and, more specifically, is related to the area of computer-assisted quantitative analysis of CT scans for bone mineral density and MRI for quantification of tissue with or without magnetic contrast agents, and digital radiography for bone density and other tissue measurements.
2 Description of the Prior Art
Computerized tomography (CT) is an imaging technique that uses an array of detectors to collect x-ray attenuation data from x-ray beams that pass through an object, such as a human body. The rotation of the x-ray beams and associated detectors about the object produces the equivalent of a "slice" through an area of interest, i.e., a planar cross-section of the human body. The x-ray attenuation data is collected as the x-ray beams are rotated and is input as digital data to a CT system computer. Specifically, computer algorithms programmed in the CT system computer process the digital attenuation data to reconstruct planar cross-sectional images of the "internal structures" through which the x-ray beams pass. The resulting reconstructed cross-sectional images are displayed on a video monitor, or the like. The reconstructed images inherently contain quantitative information about the x-ray attenuation of the internal structure of the object. Until recently, technical difficulties have prevented the full evaluation of the quantitative information.
Magnetic resonance imaging (MRI) is another technique that is developing wide acceptance in the medical imaging field. MRI relies on the principle that hydrogen atoms, when subjected to a magnetic field, become aligned. When a radio frequency signal is directed at the hydrogen atoms, the alignment of the nuclei of the atoms is changed. When the radio frequency signal is turned off, the nuclei realign in accordance with the magnetic field, and, at the same time transmit a small electric signal. The transmitted electric signals are received and converted into an image that is indicative of the hydrogen atoms that transmitted the signals. The strength of the image is analyzed to determine the densities of the hydrogen atoms and thus to determine the type of tissue corresponding to the image. Since MRI analyzes hydrogen content, it is particularly useful for analyzing soft tissues, such as the tissues of the brain. Although the invention is discussed below in connection with the use of CT systems to analyze bone mineral content, the invention is also applicable to MRI and other systems that provide images having image intensities that vary in accordance with the content of the tissue being scanned.
The CT technique was introduced by G. N. Hounsfield in 1972 to provide an enhanced, non-invasive way of imaging internal structures of an object, such as a human body. The technique is widely used for many diagnostic procedures throughout the human body, providing superior differentiation of "relative" attenuation of neighboring structures within the CT slice. The CT technique however has been ineffective for providing "absolute" attenuation measurements due to a variety of technical factors. This problem has more recently been overcome by scanning reference calibration samples simultaneously with the body of a patient, thus providing a standard for absolute calibration of tissue density, such as bone density for assessment of osteoporosis.
Osteoporosis is the most common disorder of the human skeletal system, affecting up to 32 percent of women and 17 percent of men, depending upon the age group under consideration. Basically, osteoporosis is a disease process in which the mineral content (i.e., calcium content) of a person's skeletal system is gradually reduced, leading to higher risks for fractures, particularly in the spine, hip and wrist. Osteoporosis is a major medical problem. It has been estimated that approximately 40,000 American women die per year from complications due to osteoporosis.
Osteoporosis, until recently, was considered to be undiagnosable prior to the onset of symptoms and untreatable, once it became symptomatic. Thus, it was frequently called the "silent disease."One of the many benefits obtained from the CT technique is its ability to isolate a volume of purely trabecular bone from surrounding hard cortical bone deep within the body, for example in a person's vertebrae. It has been found that the early stages of osteoporosis are characterized by early mineral loss in the trabecular bone of the spine. This is due primarily to the high metabolic turnover rate of trabecular bone that is about eight times higher than the turnover rate of cortical bone, the hard bone making up most of the skeletal system. Thus, a determination of the mineral content of the trabecular bone of the spine can be used for early detection of osteoporosis and can also be used to assess the effectiveness of therapies for prevention or reduction of further loss of mineral content in a person's bones.
Briefly, the CT technique is used to provide an image of a cross-section of a person's vertebrae, typically in the lumbar spine. The cross-section includes both the cortical (hard) bone of the vertebrae and the inner, more porous, trabecular bone. In addition, the cross-section includes various soft tissues of the surrounding body. As is well-known in the CT art, the intensity in a particular region of the CT image is directly related to the x-ray attenuation of that region of the internal structure of the body that corresponds to the same region in the image. As is well known in the art, the image comprises a two-dimensional display of pixels or voxels representing the attenuation properties of the internal structures. Each of the pixels has an intensity that corresponds to the attenuation of the x-rays by the corresponding region of the body structure. Typically, the intensity range, represented by attenuation of a portion of the image is measured in Hounsfield units (HU's). For example, the image produced as a result of the attenuation of x-rays by pure water has been assigned by convention to 0 HU; the image of air has been assigned - 1000 HU; the image of hard cortical bone may vary up to the maximum range of +1000 HU. Thus, essentially any naturally occurring portion of the human body will attenuate the x-rays such that the resulting CT image will have an intensity representing an attenuation within the range of .+-.1000 HU. For example, the attenuation caused by dense bone may produce approximately 600-800 HU, while the attenuation caused by muscle, soft tissue and fat may vary in the range of +50 to -150 HU. Trabecular bone may vary widely, having an attenuation in the range of 50 to +300 HU, wherein an attenuation of 50 is representative of advanced osteoporosis and +300, or more, is exemplary of high trabecular bone density such as may be found in male athletes. Thus, a CT scan of a person's vertebrae can be used to isolate and measure the attenuation of the x-rays in the trabecular bone such that the mineral content of the trabecular bone can be determined, and thus the "health" of the patient's bones can thereby be determined.
It has been found however that the attenuation images produced in a CT apparatus vary significantly in response to a number of technical factors of the apparatus as well as the magnitude of errors caused by beam hardening and scattered radiation within the human body. For example, the effective energy of the x-ray beams and therefore beam hardening is different between different CT machines and dependent upon the x-ray tube and filtration. Thus, the image produced by one machine may visually appear similar to the image of the same patient produced on a different machine; however, the two images may produce significantly different "absolute" quantitative attenuation values. Furthermore, the x-ray tube of a CT apparatus is subject to changes with aging and with respect to the voltage applied to the x-ray source which may have long term and short term fluctuations with respect to time. In addition, scattered radiation varies with patient size and muscle/fat ratio, and varies with detector and collimator designs. Thus, an image taken with the same machine at different times or on different machines may vary irrespective of the variations in the internal structure of the patient's body. Thus, simple extraction of the pixel intensity from the image is not sufficient to provide reliable quantitative information regarding the mineral content of the trabecular bone.
The foregoing problem was recognized a number of years ago, and a reference standard was developed to quantitatively calibrate the image produced by the CT technique. The reference standard (referred to herein as a "calibration phantom") is disclosed in U.S. Pat. No. 4,233,507 to Donald J. Volz, which is incorporated herein by reference. Basically, the original calibration phantom includes a plurality of reference samples (for example, five), each of which comprises a material having known, fixed x-ray attenuation characteristics. For example, the reference samples may be liquid-filled containers, or cavities, located in a surrounding support structure. The liquids may be solutions of dipotassium hydrogen phosphate (K.sub.2 HPO.sub.4), or, alternatively, may be solid plastic support material with homogeneously mixed calcium carbonate (CaCO.sub.3), or calcium hydroxyapatite (Ca.sub.5 (PO.sub.4).sub.3 (OH) powders, or the like. The samples are longitudinally disposed with respect to the patient and x-ray table, and are scanned simultaneously with the patient such that any slice through the patient also includes the cross-sectional images of the reference samples. The concentrations of the reference samples are selected to provide x-ray attenuations that simulate the attenuations of human bone or, alternatively, other human tissues. For example, in one exemplary embodiment of a calibration phantom having five reference samples, one of the reference samples comprises a solid having an approximate attenuation of - 100 HU similar to fat; a second reference sample may comprise a solution having an a known fixed concentration of 0 mg/cc of K.sub.2 HP0.sub.4 in pure water; a third reference solution may comprise a solution having a concentration of 50 mg/cc of K.sub.2 HP0.sub.4 in pure water; a fourth reference sample may comprise a solution having a concentration of 150 mg/cc of K.sub.2 HP0.sub.4 in pure water; and the fifth reference sample may comprise a solution having a concentration of 200 mg/cc of K.sub.2 HP0.sub.4 in pure water. Thus, the first mentioned reference sample may simulate human body fat, and the other four reference samples may represent bone densities. An exemplary calibration phantom may also include a pair of metallic rods having an attenuation of 300-800 HU that can be used in some systems to locate the aforementioned cavities. An improved version of such a calibration phantom is described in copending U.S. patent application Ser. No. 015,047, filed on Feb. 17, 1987, entitled CALIBRATION PHANTOM FOR COMPUTER TOMOGRAPHY SYSTEM. The copending application is assigned to the assignee of this application, and is incorporated herein by reference.
In an exemplary prior art system, the calibration phantom is used to provide a reference by which the attenuation of the x-rays by the internal structures of the human body can be determined. Since the attenuations of the reference sample materials in each of the cavities is precisely known, the pixel intensities recorded in the images produced by x-ray attenuation in the reference samples and in the body structures, such as bone, can be recorded and compared to the known concentrations of the reference samples. A calibration relationship (i.e., a calibration factor) can then be calculated based upon the known concentrations of the calibration reference samples and the measured intensities of the images of the calibration reference samples. The calculated calibration relationship can then be applied to the measured intensities of the images of the internal structures of the body (e.g., the trabecular bone) and the absolute attenuation of each of the structures can then be determined and referenced to the standard of the calibration phantom in mg/cc of K.sub.2 HPO.sub.4 bone density equivalence. Thus, the calibration phantom provides a way of determining the precise attenuation caused by a body structure irrespective of any deviations or fluctuations in the CT apparatus or due to biological variations from patient to patient or in the same patient on repeat scans.
In early uses of the calibration phantom, the measured image intensities were acquired by manual techniques. The operator of the CT system was required to define a region of interest (ROI) on the video display of the image of the calibration phantom. The region of interest ideally encompasses a substantial portion of the pixels that represent the image of one of the aforementioned reference samples. Each of the pixels within the region of interest has an intensity corresponding to the attenuation of the calibration material of the reference sample. Thus, the CT system computer can evaluate the intensity of the pixels and calculate the average intensity of the pixels within the region of interest. The measured intensity is then related to the known concentration of the reference sample by using linear regression analysis. All measured intensities are therefore related back to known, fixed standards of bone equivalence density. See, for example, Christopher E. Cann, et al., "Precise Measurement of Vertebral Mineral Content Using Computed Tomography,"Journal of Computer Assisted Tomography, Vol. 4, No. 4, August 1980, pp. 493-500; and Christopher E. Cann, "Low-Dose CT Scanning for Quantitative Spinal Mineral Analysis," RADIOLOGY. Vol. 140, No. 3, September 1981, pp. 813-815; both of which are incorporated herein by reference.
Typically, the region of interest (ROI) may be an approximately circular region of the video image that is graphically displayed by a bright outline on the video monitor. The ROI is adjusted for size and is positioned in the image of the reference sample by manually moving the ROI outline until it is positioned wholly within the reference sample image. The ROI outline can be moved by cursor control from a keyboard, manipulating a mouse or joystick, by manipulating a light pen, by entering coordinates from the keyboard, or other known manual procedures. Such manual procedures have been found to be very laborious and time consuming. The manual procedures are also subject to error caused by misplacement of the ROI such that it is not wholly within the portion of the image representing the reference sample. When this occurs, some of the pixels within the ROI may represent portions of the calibration phantom having a different attenuation than the attenuation of the calibration material comprising the reference sample. Thus, the measured intensities will not be correctly representative of the known concentrations of the reference samples, resulting in incorrect determinations of the equivalent densities of the various body structures. These problems are further aggravated because the operator must position an ROI for each of the plurality of calibration reference samples on multiple image slices for each patient, thus increasing the probability that one or more of the measurements will be incorrect. A similar problem occurs when the operator is positioning the ROI in the portion of the image representing the trabecular bone in the spine of the patient or other tissue areas to be quantized. It is important that the ROI encompass a substantial portion of the trabecular bone so that the averaged attenuation will more nearly represent the bone or tissue density. At the same time, it is important that the ROI not encompass the more dense cortical bone, as the attenuation of the cortical bone will distort the measurements of attenuation of the trabecular bone. Furthermore, since one of the primary purposes of the measurements is to monitor the mineral content of the trabecular bone over extended periods of time, it is important that the measurements be reproducible and less subject to changes or errors caused by variable manual procedures and human error. Thus, a need exists for a system for automating the positioning of the ROI's on a CT image.